|
|
 Previous Article | Table of Contents | Next Article 
Granulocyte-macrophage colony-stimulating factor is an endogenous regulator
of cell proliferation in juvenile chronic myelogenous leukemia
RJ Gualtieri, PD Emanuel, KS Zuckerman, G Martin, SC Clark, RK Shadduck, RA Dracker, J Akabutu, R Nitschke and ML Hetherington
Department of Medicine, Children's Hospital of Alabama, Birmingham.
Juvenile chronic myelogenous leukemia (JCML) is a rare myeloproliferative
disorder of early childhood that is clinically and cytogenically distinct
from the well-recognized adult type of chronic myeloid leukemia. Unlike the
adult disease, growth of hematopoietic progenitors from peripheral blood
(PB) occurs in the absence of exogenous stimulus even at low cell
densities. This so-called "spontaneous" growth can be abrogated by adherent
cell depletion and appears to depend on production of endogenous growth
factors. We studied seven children with JCML to determine the nature of
endogenous stimulators. With isolated PB mononuclear cells (PBMNCs) and a
3H- thymidine (3H-TdR) incorporation assay, JCML cells were shown to
incorporate high levels of 3H-TdR when cultured in the absence of stimulus
even at low cell densities. When neutralizing antisera prepared against
each of the four known colony-stimulating factors (CSFs), GM-CSF, G-CSF,
M-CSF, and interleukin-3 (IL-3), as well as antisera against interleukin-1
(alpha and beta) and tumor necrosis factor (TNF) were added to these
cultures, only the antisera against recombinant human GM-CSF (rhGM-CSF)
consistently resulted in significant inhibition of cell proliferation,
achieving up to 72% inhibition of 3H-TdR incorporation in one case.
Monoclonal antibodies (MoAbs) against rhGM-CSF resulted in a similar and
highly significant degree of inhibition. A marked inhibitory effect of
rhGM-CSF antiserum on "spontaneous" growth of PB CFU-GM derived colonies in
semisolid medium was also demonstrated in four of five patients studied
(87% to 90% inhibition). Production of growth factors by highly enriched
JCML monocytes was variable. When initially studied in five of the seven
patients, the monocytes from three of the patients revealed increased
release of IL-1-like activities; two patients had levels similar to those
of controls. One patient with normal levels when initially studied was
later shown to have markedly increased amounts of IL-1-like activities in a
second preparation of monocyte-conditioned medium (MCM). High levels of
GM-CSF were detected in the initial MCM from one patient, but this may have
indirectly reflected elevated IL-1-like activities present in the MCM. IL-3
and M-CSF levels were either low or undetectable in the patients studied as
compared with MCM prepared with normal adult monocytes. These results
clearly implicate GM-CSF as the primary endogenous regulator of JCML cell
proliferation in culture and suggest that this malignant myeloproliferative
disease may in part result from paracrine stimulation of marrow progenitor
cells by growth factors/cytokines secreted by the malignant monocytes.
Volume 74,
Issue 7,
pp. 2360-2367,
11/15/1989
Copyright © 1989 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
P. O. Iversen, P. D. Emanuel, and M. Sioud
Targeting Raf-1 gene expression by a DNA enzyme inhibits juvenile myelomonocytic leukemia cell growth
Blood,
May 13, 2002;
99(11):
4147 - 4153.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. H. Tomasson, I. R. Williams, S. Li, J. Kutok, D. Cain, S. Gillessen, G. Dranoff, R. A. Van Etten, and D. G. Gilliland
Induction of myeloproliferative disease in mice by tyrosine kinase fusion oncogenes does not require granulocyte-macrophage colony-stimulating factor or interleukin-3
Blood,
March 1, 2001;
97(5):
1435 - 1441.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. D. Emanuel, R. C. Snyder, T. Wiley, B. Gopurala, and R. P. Castleberry
Inhibition of juvenile myelomonocytic leukemia cell growth in vitro by farnesyltransferase inhibitors
Blood,
January 15, 2000;
95(2):
639 - 645.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. O. Iversen and M. Sioud
Modulation of Granulocyte-Macrophage Colony-Stimulating Factor Gene Expression by a Tumor Necrosis Factor alpha Specific Ribozyme in Juvenile Myelomonocytic Leukemic Cells
Blood,
December 1, 1998;
92(11):
4263 - 4268.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y.-Y. Zhang, T. A. Vik, J. W. Ryder, E. F. Srour, T. Jacks, K. Shannon, and D. Wade Clapp
Nf1 Regulates Hematopoietic Progenitor Cell Growth and Ras Signaling in Response to Multiple Cytokines
J. Exp. Med.,
June 1, 1998;
187(11):
1893 - 1902.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Sawai, K. Koike, T. Higuchi, K. Ogami, and M. Oda
Thrombopoietin Enhances the Production of Myeloid Cells, but not Megakaryocytes, in Juvenile Chronic Myelogenous Leukemia
Blood,
June 1, 1998;
91(11):
4065 - 4073.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. O. Iversen, I. D. Lewis, S. Turczynowicz, H. Hasle, C. Niemeyer, K. Schmiegelow, S. Bastiras, A. Biondi, T. P. Hughes, and A. F. Lopez
Inhibition of Granulocyte-Macrophage Colony-Stimulating Factor Prevents Dissemination and Induces Remission of Juvenile Myelomonocytic Leukemia in Engrafted Immunodeficient Mice
Blood,
December 15, 1997;
90(12):
4910 - 4917.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. P. McCormack and T. J. Gonda
Expression of Activated Mutants of the Human Interleukin-3/Interleukin-5/Granulocyte-Macrophage Colony-Stimulating Factor Receptor Common beta Subunit in Primary Hematopoietic Cells Induces Factor-Independent Proliferation and Differentiation
Blood,
August 15, 1997;
90(4):
1471 - 1481.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C.M. Niemeyer, M. Arico, G. Basso, A. Biondi, A. C. Rajnoldi, U. Creutzig, O. Haas, J. Harbott, H. Hasle, G. Kerndrup, et al.
Chronic Myelomonocytic Leukemia in Childhood: A Retrospective Analysis of 110 Cases
Blood,
May 15, 1997;
89(10):
3534 - 3543.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Freedman, J. Hitzler, N Bunin, T Grunberger, and J Squire
Juvenile chronic myelogenous leukemia multilineage CD34+ cells: aberrant growth and differentiation properties
Stem Cells,
November 1, 1996;
14(6):
690 - 701.
[Abstract]
|
|
|
|
|
|
|
R. P. Castleberry, P. D. Emanuel, K. S. Zuckerman, S. Cohn, L. Strauss, R. L. Byrd, A. Homans, S. Chaffee, R. Nitschke, and R. J. Gualtieri
A Pilot Study of Isotretinoin in the Treatment of Juvenile Chronic Myelogenous Leukemia
N. Engl. J. Med.,
December 22, 1994;
331(25):
1680 - 1684.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
Literature Review: References of Interest for the Pediatric Oncology Nurse
Journal of Pediatric Oncology Nursing,
January 1, 1990;
7(3):
122 - 125.
[PDF]
|
|
|
|
|
